Regulated Assembly of Subcellular Structures in alpha-Proteobacteria

描述（由申请人提供）：细菌细胞已经进化出多种调节机制，以确保其亚细胞结构和细胞器，如毛和鞭毛，被正确地组装和定位。我们的目标是确定一个保守调控系统的核心组成部分，以及它们之间的相互作用，是如何适应不同生物体的特殊需求的。在新月形茎杆菌中，该调节系统的蛋白质成分（PodJ、DivJ和PleC）遵循亚细胞定位的确定模式，导致细胞形态不对称：细胞器特异性地在一端发育，而在另一端不发育。调控成分在Sinorhizobium meliloti中是保守的，Sinorhizobium meliloti是一种在共生过程中诱导植物根系形成根瘤的相关细菌。然而，与月牙草相比，S. meliloti细胞在形态上是对称的。我们将研究这些保守成分如何在S. meliloti中调节表面细胞器的组装以及这种调节如何影响宿主-微生物的相互作用。(1)我们将首先确定调节蛋白的定位模式和缺乏这些蛋白的零突变体的表型。(2)然后，我们将检测和分析突变体转录谱的变化，看看这些蛋白质是否控制着不同物种中相似基因的表达。(3)我们还将评估突变是否会破坏细菌与其宿主之间的相互作用，从而阻止有效结瘤。除了这些研究目标外，在资深科学家的指导下，主要研究者还希望实现以下发展目标：(4)建立独立的研究小组；(5)提高指导技能；(6)提高研究质量。

DESCRIPTION (provided by applicant): Bacterial cells have evolved multiple regulatory mechanisms to ensure that their subcellular structures and organelles, such as pili and flagella, are assembled and positioned correctly. Our goal is to determine how the core components of a conserved regulatory system, and their interactions, have been adapted to serve the particular needs of different organisms. In Caulobacter crescentus, the protein components of this regulatory system (PodJ, DivJ, and PleC) follow defined patterns of subcellular localization that contribute to asymmetric cell morphology: organelles specifically develop at one pole but not the other. The regulatory components are conserved in Sinorhizobium meliloti, a related bacterium that induces nodule formation in plant roots during symbiosis. However, S. meliloti cells are morphologically symmetric compared to C. crescentus. We will examine how these conserved components function in S. meliloti to regulate the assembly of surface organelles and how this regulation affects host-microbe interaction. (1) We will first determine the localization patterns of the regulatory proteins and the phenotypes of null mutants that lack the proteins. (2) We will then detect and analyze changes in the mutants' transcriptional profiles to see if the proteins control expression of similar genes in different species. (3) We will also assess whether the mutations disrupt interaction between the bacterium and its hosts, preventing effective nodulation. In addition to these research objectives, the principal investigator aims to achieve the following developmental objectives under the guidance of a senior scientist: (4) establish an independent research group, (5) enhance mentoring skills, and (6) improve the quality of research. Relevance to Public Health: The proposed research is expected to reveal the driving principles of a regulatory pathway that exists in multiple bacterial species, including pathogens. Components of the pathway may serve as targets for new antimicrobial compounds.